Drug administration by topical skin application of a drug offers distinct advantages over conventional administration methods. For example, some drugs cannot be absorbed in the digestive tract and intravenous and subcutaneous administration by injection is inconvenient and invasive. Oral and intravenous administration for treatment of a localized skin condition is undesirable as the drug is circulated systemically rather than restricted to the localized, diseased area. Yet, due to the protective nature of skin serving its intended function of being resistant to external perturbations, only a limited number of drugs are bioavailable via topical application.
Drug administration via the skin may be transdermal or intradermal (also referred to as local or dermal). Transdermal administration involves transport through the skin such that a therapeutic amount of the drug is achieved in the systemic blood circulation. Intradermal or topical administration of a drug involves entry of the drug across the stratum corneum for a cutaneous or local skin effect; that is the pharmacological effect of the drug is localized to the intracutaneous regions of drug penetration and deposition. Preferably, intradermal absorption occurs with little or no systemic absorption or accumulation. Intradermal absorption of a drug involves partitioning of the drug from the applied vehicle into the stratum corneum; diffusion of the drug through the stratum corneum; and partitioning of the drug from the stratum corneum into the epidermis. In contrast, transdermal absorption further involves diffusion of the drug through the epidermis; and capillary uptake of the drug for circulation in the blood.
Whereas transdermal compositions are intended to deliver drugs for systemic circulation, a different composition would be needed to deliver the same drug intracutaneously. Topical formulations that achieve delivery of a drug across the stratum corneum and retention of the majority of the drug dermally such that it does not enter the blood stream in significant amounts are complicated to design and require innovative approaches. Several factors determine the permeability of the skin or of specific layers, in particular the stratum corneum, of the skin to drug compounds. These factors include the characteristics of the skin, the characteristics of the drug compound (e.g., its size (molecular weight or molecular volume), its lipophilicity/hydrophilicity, its polarity), the dosage of the drug compound applied, interactions between the drug compound and the delivery vehicle, interactions between the drug compound and the skin, and interactions of the drug and the skin in the presence of the ingredients in the delivery vehicle. As a result of the multitude of factors involved in administration of a drug intracutaneously, it is generally accepted that whether intracutaneous delivery of a drug compound can be achieved in an amount sufficient for therapy is uncertain. Penetration enhancers are commonly used in transdermal delivery to achieve penetration of a drug across the stratum corneum typically to provide for systemic delivery of the drug, rather than its retention in the epidermis or dermis. Thus, topical administration, while desired from a patient convenience and drug delivery view, has been largely unsuccessful for many compounds as evidenced by the relatively few drugs approved for topical administration.
A condition that would benefit from a topical formulation that achieves intracutaneous delivery of a drug is basal cell carcinoma (BCC), the most common form of skin cancer in the United States. BCC is observed in the general population typically on sun-exposed areas of the skin, and in subjects with the Basal Cell Nevus Syndrome, also known as Gorlin syndrome, an inherited condition where the skin is prone to developing BCCs. Although BCCs rarely spread (i.e., metastasize) to other parts of the body, they can be destructive and disfiguring. A variety of surgical and non-surgical therapies are available for BCCs. Nonsurgical therapies include radiation therapy, chemotherapy, and immunotherapy. These therapies can be useful for definitive treatment of primary tumors and some recurrent BCC tumors and for relieving symptoms associated with inoperable tumors. However, some of these therapies also can have significant unpleasant side effects. Side effects of radiation therapy and certain chemotherapies are well documented. One form of immunotherapy involves intralesional injections of interferon. While interferon therapy can be effective against BCC, the multiple intralesional injections can require several clinic visits per week for many weeks and are painful. Thus, there remains a need for a non-surgical therapy for BCC that offers better patient convenience.
The foregoing examples of the related art and limitations related therewith are intended to be illustrative and not exclusive. Other limitations of the related art will become apparent to those of skill in the art upon a reading of the specification and a study of the drawings.